Two common cardiac biomarkers may help improve risk prediction among patients with nonvalvular atrial fibrillation, a RE-LY substudy showed.

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Two common cardiac biomarkers, troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), may help improve risk prediction among patients with nonvalvular atrial fibrillation.

Note that elevations of both biomarkers were associated with greater risks of stroke or systemic embolism, vascular mortality, and a composite of thromboembolic events.

Two common cardiac biomarkers -- troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) -- may help improve risk prediction among patients with nonvalvular atrial fibrillation, a RE-LY substudy showed.

Elevations of both biomarkers were associated with greater risks of stroke or systemic embolism, vascular mortality, and a composite of thromboembolic events, according to Ziad Hijazi, MD, of Uppsala University in Sweden, and colleagues.

High troponin I levels also were associated with increased risks of myocardial infarction (MI) and major bleeding, the researchers reported online in Circulation: Journal of the American Heart Association.

Inclusion of the two biomarkers added prognostic value to established risk assessments, including the CHADS2 and CHA2DS2-VASc scores.

"Patients with high CHADS2 or CHA2DS2-VASc risk score and elevated cardiac biomarkers remain at high risk for thromboembolic events despite preventive treatment with effective oral anticoagulants," the authors wrote.

Troponin I and NT-proBNP, which are markers of myocardial cell damage and myocardial wall tension, respectively, have been associated with mortality and morbidity in patients with acute coronary syndromes, stable coronary disease, and congestive heart failure, as well as among older individuals in the general population.

Hijazi and colleagues explored the issue in patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke who participated in the RE-LY trial, which showed that the 150-mg dose of dabigatran (Pradaxa) was better at preventing stroke than warfarin.

The substudy included 6,189 patients (median age 72), representing about one-third of the total trial population. All of the patients were receiving some form of oral anticoagulation.

The researchers divided the patients into quartiles for troponin I level and for NT-proBNP level. Troponin I was elevated in about 25% of patients and NT-proBNP was elevated in about 75% of patients.

After adjustment for cardiovascular risk factors, the annual rate of stroke or systemic embolism was significantly higher among patients with the highest troponin I levels (0.04 µg/L or higher) compared with those with undetectable levels (2.09% versus 0.84%, HR 1.99, 95% CI 1.17 to 3.39).

The relationship was similar for NT-proBNP, with an annual rate of 2.3% for patients in the highest quartile (greater than 1,402 ng/L) and 0.92% for those with levels less than 387 ng/L (HR 2.40, 95% CI 1.41 to 4.07).

Patients with elevated levels of troponin I and NT-proBNP also had significantly greater risks of vascular mortality (HRs 4.38 and 6.73, P<0.0001 for both) and a composite of thromboembolic events (HRs 3.43 and 3.55, P<0.0001 for both).

The observed associations with stroke or systemic embolism, and the composite of thromboembolic events, remained consistent within each level of risk according to traditional cardiovascular risk factors, as well as the CHADS2 and CHA2DS2-VASc scores, indicating that the addition of the two biomarkers improved risk prediction beyond existing tools.

For example, traditional cardiovascular risk factors alone yielded a C-statistic of 0.68 for the composite of thromboembolic events. Adding the two biomarkers increased the C-statistic to 0.72 (P<0.0001).

The authors noted that the findings apply only to patients with nonvalvular atrial fibrillation who have at least one additional risk factor for stroke.

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